Induction of pluripotency in mouse somatic cells with novel factors (expression)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47441 | GEO | 2013/05/28
SECONDARY ACCESSION(S): PRJNA205932
REPOSITORIES: GEO
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Project description:For years, reprogramming factors that induce pluripotency have been identified primarily from ESC-enriched factors, pluripotency-associated factors such as Oct4, Sox2, Klf4, c-Myc, Nanog, Esrrb, Sall4, Utf1, Lin28, PRDM14, and Tet2. Through genome-wide screen we identified novel regulators of reprogramming. Our study is the first proof-of-principle report to suggest a putative general mathematical model. This model provides novel mechanistic insight into the fundamental understanding of the establishment of cellular identity during programming and reprogramming. Through genome-wide screen to identify novel factors of reprogramming in addition to Oct4, Sox2, Klf4, cMyc Through genome-wide screen to identify novel factors of reprogramming in addition to Oct4, Sox2, Klf4, cMyc. Induced pluripotent stem cells versus mouse embryonic fibroblast.
2013-05-28 | E-GEOD-47441 | biostudies-arrayexpress
Project description:For years, reprogramming factors that induce pluripotency have been identified primarily from ESC-enriched factors, pluripotency-associated factors such as Oct4, Sox2, Klf4, c-Myc, Nanog, Esrrb, Sall4, Utf1, Lin28, PRDM14, and Tet2. Through genome-wide screen we identified novel regulators of reprogramming. Our study is the first proof-of-principle report to suggest a putative general "seesaw model". This model provides novel mechanistic insight into the fundamental understanding of the establishment of cellular identity during programming and reprogramming. Through genome-wide screen to identify novel factors of reprogramming in addition to Oct4, Sox2, Klf4, cMyc.
2013-05-28 | E-GEOD-47442 | biostudies-arrayexpress
Project description:For years, reprogramming factors that induce pluripotency have been identified primarily from ESC-enriched factors, pluripotency-associated factors such as Oct4, Sox2, Klf4, c-Myc, Nanog, Esrrb, Sall4, Utf1, Lin28, PRDM14, and Tet2. Through genome-wide screen we identified novel regulators of reprogramming. Our study is the first proof-of-principle report to suggest a putative general "seesaw model". This model provides novel mechanistic insight into the fundamental understanding of the establishment of cellular identity during programming and reprogramming.
2013-05-28 | GSE47442 | GEO
Project description:PRDM14 belongs to the PR (PRDI-BF1 and RIZ) domain proteins (PRDM) family which is a subclass of the SET domain proteins, a common domain found in histone modifying enzymes. PRDM14 has been previously implicated to regulate self-renewal of hESCs as knock-down of PRDM14 induced expression of differentiation marker genes and altered the cellular morphology. We showed that PRDM14 directly regulates the expression of key pluripotency gene POU5F1. Genome-wide location profiling experiments revealed that PRDM14 co-localized extensively with other key transcription factors such as OCT4, NANOG and SOX2. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Hence, PRDM14 exemplifies a key transcription factor that is required for the maintenance of human ESC identity and the reacquisition of pluripotency in human somatic cells. ChIP-seq of PRDM14 in human ESCs
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Project description:PRDM14 belongs to the PR (PRDI-BF1 and RIZ) domain proteins (PRDM) family which is a subclass of the SET domain proteins, a common domain found in histone modifying enzymes. PRDM14 has been previously implicated to regulate self-renewal of hESCs as knock-down of PRDM14 induced expression of differentiation marker genes and altered the cellular morphology. We showed that PRDM14 directly regulates the expression of key pluripotency gene POU5F1. Genome-wide location profiling experiments revealed that PRDM14 co-localized extensively with other key transcription factors such as OCT4, NANOG and SOX2. More importantly, in a gain-of-function assay, we showed that PRDM14 is able to enhance the efficiency of reprogramming of human fibroblasts in conjunction with OCT4, SOX2 and KLF4. Hence, PRDM14 exemplifies a key transcription factor that is required for the maintenance of human ESC identity and the reacquisition of pluripotency in human somatic cells.
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Project description:Since the initial discovery that OCT4, SOX2, KLF4 and c-MYC overexpression sufficed for the induction of pluripotency in somatic cells, methodologies replacing the original factors have enhanced our understanding of the reprogramming process. However, unlike in mouse, OCT4 has not been replaced successfully during reprogramming of human cells. Here we report on a strategy to do so. Through a combination of transcriptome and bioinformatic analysis we have identified factors previously characterized as being lineage specifiers that are able to replace OCT4 and SOX2 in the reprogramming of human fibroblasts. Our results show that is possible to replace OCT4 and SOX2 simultaneously with alternative lineage specifiers in the reprogramming of human cells. At a broader level, they also support a model in which counteracting lineage specification networks underlie the induction of pluripotency, We analyzed 3 arrays from human fibroblats; 1 array from 4F iPSC; 1 array from 4F iPSC; 1 array for GATA3SOX2, KLF4 and cMYC iPS; 1 array for GATA3vP16,SOX2VP16, KLF4 and cMYC iPS;1 array for GATA3vP16SOX2VP16, KLF4 and cMYC iPS; 1 array for GATA3vP16SOX2VP16, KLF4 and cMYC iPS; 1 array for hES4;1 array for hES10; 1 arrays for iPS generated with OCT4, ZIC2, ZNF521, ASCL1, HESX1,FOXD5,KLF4 and cMYC; 1 arrays for iPS generated with OCT4, ZIC2, ZNF521, ASCL1, HESX1,FOXD5,KLF4 and cMYC; 1 array for iPS generated with OCT4, SOX1, KLF4 and cMYC;1 array for iPS generated with OCT4, SOX1, KLF4 and cMYC;1 array for iPS generated with OCT4, ZNF521, KLF4 and cMYC: 1 array for iPS generated with OCT4, SOX3, KLF4 and cMYC
2013-12-31 | E-GEOD-48275 | biostudies-arrayexpress
Project description:Human fibroblasts can be induced into pluripotent stem cells (iPS cells), but the reprogramming efficiency is quite low. Here, we screened a panel of candidate factors in the presence of OCT4, SOX2, KLF4 and c-MYC in an effort to improve the reprogramming efficiency from human adult fibroblasts. We found that p53 siRNA and UTF1 enhanced the efficiency of iPS cell generation up to 100-fold, even when the oncogene c-MYC was removed from the combinations. We further demonstrated that by using a novel combination of the four factors OCT4, SOX2, KLF4 and UTF1, iPS cells could be generated at a frequency at least 10 times higher than using the original four reprogramming factors without c-MYC. The iPS cells generated in this work have a similar gene expression profile and differentiation potential as human embryonic stem (hES) cells. In conclusion, two novel supporting factors that increase the efficiency of direct reprogramming have been identified, and a more-efficient method for the generation of human iPS cells has been developed in the absence of the oncogene c-MYC. Keywords: cell type comparison Total RNA from hFSF, hAFF, hES cells (H1, H7) and 7 established iPS cell lines were labeled with Cy5, hybridized to a human Oligo Microarray (Phalanx Human Whole Genome OneArray™, Phalanx Biotech) according to the manufacturer's protocol. Three technical repetitions were performed. After hybridization, arrays were scanned using GenePix 4000B scanner (Molecular Devices) and processed using the GenePix Pro 6.0 software (Molecular Devices). After removing control probes, a 14/33 presence call (SNR>=5 and foreground-background>0) was used to filter probes for the 33 microarrays, resulting in 12311 probes for further quantile normalization.
2008-11-06 | E-GEOD-12922 | biostudies-arrayexpress
Project description:The core pluripotency factors (Oct4, Sox2, and Nanog), the Myc network, and the chromatin-modifying complexes such as PRC2 ensure the pluripotency and self-renewal of ES cells (ESC). How these factors coordinate with one another remains poorly understood. We report that Utf1, a target of Oct4 and Sox2, is a new bivalent chromatin component that buffers poised states of bivalent genes. By limiting PRC2 loading and Histone 3 lysine-27 trimethylation, Utf1 sets proper activation thresholds for bivalent genes. It also promotes nuclear tagging of mRNAs transcribed from insufficiently silenced bivalent genes for cytoplasmic degradation through mRNA de-capping. Whereas these opposing functions of Utf1 allow proper execution of ESC pluripotency, the mRNA pruning function also ensures rapid cell proliferation by blocking the Myc-Arf feedback regulation. Thus, Utf1 is an important regulator that couples the core pluripotency factors with Myc and PRC2 networks to promote proliferation and pluripotency execution of ESCs.
2012-10-26 | GSE39513 | GEO
Project description:The core pluripotency factors (Oct4, Sox2, and Nanog), the Myc network, and the chromatin-modifying complexes such as PRC2 ensure the pluripotency and self-renewal of ES cells (ESC). How these factors coordinate with one another remains poorly understood. We report that Utf1, a target of Oct4 and Sox2, is a new bivalent chromatin component that buffers poised states of bivalent genes. By limiting PRC2 loading and Histone 3 lysine-27 trimethylation, Utf1 sets proper activation thresholds for bivalent genes. It also promotes nuclear tagging of mRNAs transcribed from insufficiently silenced bivalent genes for cytoplasmic degradation through mRNA de-capping. Whereas these opposing functions of Utf1 allow proper execution of ESC pluripotency, the mRNA pruning function also ensures rapid cell proliferation by blocking the Myc-Arf feedback regulation. Thus, Utf1 is an important regulator that couples the core pluripotency factors with Myc and PRC2 networks to promote proliferation and pluripotency execution of ESCs. First we mapped Utf1 binding sites in ESCs using the biotin-mediated and cross-linked ChIP-sequencing. To investigate how Utf1 might regulate gene expression, we did RNA-seq on WT and Utf1-KO ES cells. Then we did ChIP-seq of Suz12 and H3K27me3 on WT and Utf1-KO ES cells to study whether Utf1 affects PRC2 loading and H3K27me3 modofication, using H3 as control. Finally, we did RNAseq on WT and Dcp1a-KD ES cells to confirm Utf1 repress gene expression by recruiting Dcp1a complex.
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